Invasive Group A Streptococcal Infections: Benefit of Clindamycin, Intravenous Immunoglobulins and Secondary Prophylaxis

Abstract

Introduction: Mortality associated with invasive group A streptococcal infections (iGAS) remains high among adults, with lower mortality in children. The added value of both clindamycin and immunoglobulins in such treatment is still controversial, as is the need for antibiotic secondary prophylaxis. It is unlikely that conclusive randomized clinical studies will ever definitively end these controversies.Materials and Methods: A clinical and experimental literature review was conducted in Pubmed, Cochrane, and lay literature to determine the benefit of adding clindamycin and immunoglobulins to β-lactams in the management of iGAS, as well as the need for secondary prophylaxis measures in close contacts.Results: This review includes two meta-analyses, two randomized controlled trials, four prospective studies, five retrospective studies, and microbiological studies. To reduce mortality and morbidity, it appears useful to add clindamycin to β-lactams in severe clinical presentations, including necrotizing fasciitis or streptococcal toxic shock syndrome, and immunoglobulins for the latter two presentations. The high risk of secondary infection in household contacts justifies the need of taking preventive measures.Conclusions: Both clinical studies and available experimental evidence suggest that adding clindamycin and immunoglobulins as adjunctive therapies in the management of invasive group A streptococcal infections may reduce mortality. Household contacts should be warned about the increased risk of secondary infection, and chemoprophylaxis may be considered in certain situations.

Dihydrothiazolo ring-fused 2-pyridone antimicrobial compounds treatStreptococcus pyogenesskin and soft tissue infection

“…However, this therapeutic approach is being rendered less effective by rising rates of clindamycin resistance. Another approach has been to use passive immunotherapy with intravenous pooled human immunoglobulin (IVIG) (44) pyogenes HSC5 strain (39,46) whose virulence properties in the murine SSTI has been extensively characterized (8,9,47). Unless otherwise specified, liquid cultures utilized C medium (39) and were inoculated from several colonies picked from a C medium plate that had been incubated overnight at 37 o C under the anaerobic conditions produced by a commercial anaerobic generator (Becton Dickinson, 260683).…”

“…However, this therapeutic approach is being rendered less effective by rising rates of clindamycin resistance. Another approach has been to use passive immunotherapy with intravenous pooled human immunoglobulin (IVIG) ( 44 ) which may both neutralize toxins and promote neutralization of antiphagocytic and biofilm-promoting virulence factors such as M protein. Thus, the ability of GmPcides to inhibit expression of SpeB, M protein and other virulence factors may have contributed to PS757’s ability to treat SSTI by reducing tissue damage, accelerating bacterial clearance, stimulating ulcer healing, and alleviating host inflammation to promote a quicker recovery.…”

Case Report: Therapeutic Strategy With Delayed Debridement for Culture-Negative Invasive Group A Streptococcal Infections Diagnosed by Metagenomic Next-Generation Sequencing

“…Clindamycin also has non-antimicrobial antibiotic effects such as the inhibition of M-protein synthesis, superantigens and other toxins ( 35 ). Clindamycin, together with β-lactams, is considered to be effective in the treatment of necrotizing fasciitis or STSS ( 35 , 36 ). An Australian prospective study suggested that adding clindamycin could reduce mortality ( 37 ).…”

“…Disappointingly, the result of the trial showed no significant effects of adjuvant IVIG on self-reported physical functioning at 6 months, mortality or organ failure. Despite the controversy, regarding the efficacy and the low risk of side effects, IVIG is still recommended for treatment in patients with unstable hemodynamics and/or having STSS or necrotizing fasciitis ( 36 , 46 , 47 ). Additionally, the timing of administration is crucial because this treatment only offers short-term protection and does not induce active immunity.…”

Streptococcal toxic shock syndrome with associated necrotising fasciitis necessitating amputation of the lower extremity – A case report

“…8 Several clinical and experimental studies have shown that treatment with penicillin, clindamycin and immunoglobulins can reduce morbidity and mortality in patients with STSS. 9 The aim of this case report is to describe the complex clinical presentation of STSS, highlight therapeutic options, illuminate different treatment pathways and present a successful outcome as a lighthouse case to help other medical professionals decide on the choice of therapy after a full investigation (including laboratory chemistry, microbiology and radiology). In this context, the present case report confirms the already known newer literature, adapts it to the clinical context and emphasises the rapid and time-critical interdisciplinary clinical cooperation.…”